| Autor: |
Flores C; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK., Ling J; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK., Loh A; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK., Maset RG; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK., Aw A; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK., White IJ; Laboratory for Molecular Cell Biology, University College London, WC1E 6BT London, UK., Fernando R; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK.; Royal Free London NHS Foundation Trust & Anthony Nolan Laboratories, NW3 2QG London, UK., Rohn JL; Centre for Urological Biology, Division of Medicine, University College London, WC1E 6BT London, UK. |
| Abstrakt: |
Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli , suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus . Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level. |
